Browsing by Author "Kundra, R."

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Open Access
Abstract 207: the cBioPortal for cancer genomics
(American Association for Cancer Research (AACR), 2021) Gao, J.; Mazor, T.; de Bruijn, I.; Abeshouse, A.; Baiceanu, D.; Erkoç, Z.; Gross, B.; Higgins, D.; Jagannathan, P. K.; Kalletla, K.; Kumari, Priti; Kundra, R.; Li, X.; Lindsay, J.; Lisman, A.; Lukasse, P.; Madala, D.; Madupuri, R.; Ochoa, A.; Plantalech, O.; Quach, J.; Rodenburg, S.; Satravada, A.; Schaeffer, F.; Sheridan, R.; Sikina, L.; Sümer, S. O.; Sun, Y.; van Dijk, P.; van Nierop, P.; Wang, A.; Wilson, M.; Zhang, H.; Zhao, G.; van Hagen, S.; van Bochove, K.; Doğrusöz, Uğur; Heath, A.; Resnick, A.; Pugh, T. J.; Sander, C.; Cerami, E.; Schultz, N.
The cBioPortal for Cancer Genomics is an open-source software platform that enables interactive, exploratory analysis of large-scale cancer genomics data sets with a user-friendly interface. It integrates genomic and clinical data, and provides a suite of visualization and analysis options, including OncoPrint, mutation diagram, variant interpretation, survival analysis, expression correlation analysis, alteration enrichment analysis, cohort and patient-level visualization, among others.The public site (https://www.cbioportal.org) hosts data from almost 300 studies spanning individual labs and large consortia. Data is also available in the cBioPortal Datahub (https://github.com/cBioPortal/datahub/). In 2020 we added data from 21 studies, totaling almost 30,000 samples. In addition, we added data to existing TCGA PanCancer Atlas studies, including MSI status, mRNA-seq z-scores relative to normal tissue, microbiome data, and RPPA-based protein expression. The cBioPortal also supports AACR Project GENIE with a dedicated instance hosting the GENIE cohort of 112,000 clinically sequenced samples from 19 institutions worldwide (https://genie.cbioportal.org).The site is accessed by over 30,000 unique visitors per month. To support these users, we hosted a five-part instructional webinar series. Recordings of these webinars are available on our website and have already been viewed thousands of times.In addition, more than 50 instances are installed at academic institutions and pharmaceutical/biotechnology companies. In support of these local instances, we continue to simplify the installation process: we now provide a docker compose solution which includes all microservices to run the web app as well as data validation, import and migration.We continue to enhance and expand the functionality of cBioPortal. This year we significantly enhanced the group comparison feature; it is now integrated into gene-specific queries and supports comparison of more data types including DNA methylation, microbiome, and any outcome measure. We also expanded support of longitudinal data: the existing patient timeline has been refactored and now supports a wider range of data and visualizations; a new “Genomic Evolution” tab highlights changes in mutation allele frequencies across multiple samples from a patient; and samples can now be selected based on pre- or post-treatment status. Other features released this year include: allowing users to add gene-level plots for continuous molecular profiles in study view, enabling users to select the desired transcript on the Mutations tab, and integration of PathwayMapper.The cBioPortal is fully open source (https://github.com/cBioPortal/) under a GNU Affero GPL license. Development is a collaborative effort among groups at Memorial Sloan Kettering Cancer Center, Dana-Farber Cancer Institute, Children's Hospital of Philadelphia, Princess Margaret Cancer Centre, Bilkent University and The Hyve.
Open Access
Analysis and visualization of longitudinal genomic and clinical data from the AACR project GENIE biopharma collaborative in cBioPortal
(American Association for Cancer Research, 2023-12-01) de Bruijn, I.; Kundra, R.; Mastrogiacomo, B.; Tran, T. N.; Sikina, L.; Mazor, T.; Li, X.; Ochoa, A.; Zhao, G.; Lai, B.; Abeshouse, A.; Baiceanu, D.; Çiftçi, E.; Doğrusöz, Uğur; Dufilie, A.; Erkoç, Z.; Garcia Lara, E.; Fu, Z.; Gross, B.; Haynes, C.; Heath, A.; Higgins, D.; Jagannathan, P.; Kalletla, K.; Kumari, P.; Lindsay, J.; Lisman, A.; Leenknegt, B.; Lukasse, P.; Madela, D.; Madupuri, R.; van Nierop, P.; Plantalech, O.; Quach, J.; Resnick, A. C.; Rodenburg, S. Y. A.; Satravada, B. A.; Schaeffer, F.; Sheridan, R.; Singh, J.; Sirohi, R.; Sümer, S. O.; van Hagen, S.; Wang, A.; Wilson, M.; Zhang, H.; Zhu, K.; Rusk, N.; Brown, S.; Lavery, J. A.; Panageas, K. S.; Rudolph, J. E.; LeNoue-Newton, M. L.; Warner, J. L.; Guo, X.; Hunter-Zinck, H.; Yu, T. V.; Pilai, S.; Nichols, C.; Gardos, S. M.; Philip, J.; Kehl, K. L.; Riely, G. J.; Schrag, D.; Lee, J.; Fiandalo, M. V.; Sweeney, S. M.; Pugh, T. J.; Sander, C.; Cerami, E.; Gao, J.; Schultz, N.
International cancer registries make real-world genomic and clinical data available, but their joint analysis remains a challenge. AACR Project GENIE, an international cancer registry collecting data from 19 cancer centers, makes data from >130,000 patients publicly available through the cBioPortal for Cancer Genomics (https://genie.cbioportal.org). For 25,000 patients, additional real-world longitudinal clinical data, including treatment and outcome data, are being collected by the AACR Project GENIE Biopharma Collaborative using the PRISSMM data curation model. Several thousand of these cases are now also available in cBioPortal. We have significantly enhanced the functionalities of cBioPortal to support the visualization and analysis of this rich clinico-genomic linked dataset, as well as datasets generated by other centers and consortia. Examples of these enhancements include (i) visualization of the longitudinal clinical and genomic data at the patient level, including timelines for diagnoses, treatments, and outcomes; (ii) the ability to select samples based on treatment status, facilitating a comparison of molecular and clinical attributes between samples before and after a specific treatment; and (iii) survival analysis estimates based on individual treatment regimens received. Together, these features provide cBioPortal users with a toolkit to interactively investigate complex clinico-genomic data to generate hypotheses and make discoveries about the impact of specific genomic variants on prognosis and therapeutic sensitivities in cancer.
Open Access
The cBioPortal for cancer genomics and its application in precision oncology
(American Association for Cancer Research, 2016) Gao, J.; Lindsay, J.; Watt, S.; Doğrusöz, Uğur; Lukasse, P.; Abeshouse, A.; Chen, H.; Bruijn, I.; Gross, B.; Li, D.; Kundra, R.; Heins, Z.; Reis-Filho, J.; Sumer, O.; Sun, Y.; Wang, J.; Wang, Q.; Zhang, H.; Kumari, P.; Şahin, Mehmet Furkan; Ridder, S.; Schaeffer, F.; Bochove, K.; Pugh, T.; Sander, C.; Cerami, E.; Schultz, N.; Bahçeci, İstemi
Abstract The cBioPortal for Cancer Genomics provides intuitive visualization and analysis of complex cancer genomics data. The public site (http://cbioportal.org/) is accessed by more than 1,500 researchers per day, and there are now dozens of local instances of the software that host private data sets at cancer centers around the globe. We have recently released the software under an open source license, making it free to use and modify by anybody. The software and detailed documentation are available at https://github.com/cBioPortal/cbioportal. We are now establishing a multi-institutional software development network, which will coordinate and drive the future development of the software and associated data pipelines. This group will focus on four main areas: 1. New analysis and visualization features, including: a. Improved support for cross-cancer queries and cohort comparisons. b. Enhanced clinical decision support for precision oncology, including an improved patient view with knowledge base integration, patient timelines and improved tools for visualizing tumor evolution. 2. New data pipelines, including support for new genomic data types and streamlined pipelines for TCGA and the International Cancer Genome Consortium (ICGC). 3. Software architecture and performance improvements. 4. Community engagement: Documentation, user support, and training. This coordinated effort will help to further establish the cBioPortal as the software of choice in cancer genomics research, both in academia and the pharmaceutical industry. Furthermore, as the sequencing of tumor samples has entered clinical practice, we are expanding the features of the software so that it can be used for precision medicine at cancer centers. In particular, clean, web-accessible, interactive clinical reports integrating multiple sources of genome variation and clinical annotation over time has potential to improve clinical action beyond current text-based molecular reports. By making complex genomic data easily interpretable and linking it to information about drugs and clinical trials, the cBioPortal software has the potential to facilitate the use of genomic data in clinical decision making. Citation Format: Jianjiong Gao, James Lindsay, Stuart Watt, Istemi Bahceci, Pieter Lukasse, Adam Abeshouse, Hsiao-Wei Chen, Ino de Bruijn, Benjamin Gross, Dong Li, Ritika Kundra, Zachary Heins, Jorge Reis-Filho, Onur Sumer, Yichao Sun, Jiaojiao Wang, Qingguo Wang, Hongxin Zhang, Priti Kumari, M. Furkan Sahin, Sander de Ridder, Fedde Schaeffer, Kees van Bochove, Ugur Dogrusoz, Trevor Pugh, Chris Sander, Ethan Cerami, Nikolaus Schultz. The cBioPortal for cancer genomics and its application in precision oncology. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5277.
Open Access
Oncogenic signaling pathways in the Cancer Genome Atlas
(Cell Press, 2018) Sanchez-Vega, F.; Mina, M.; Armenia, J.; Chatila, W. K.; Luna, A.; La, K. C.; Dimitriadoy, S.; Liu, D. L.; Kantheti, H. S.; Saghafinia, S.; Chakravarty, D.; Daian, F.; Gao, Q.; Bailey, M. H.; Liang, W. -W.; Foltz, S. M.; Shmulevich, I.; Ding, L.; Heins, Z.; Ochoa, A.; Gross, B.; Gao, J.; Zhang, H.; Kundra, R.; Kandoth, C.; Bahceci, I.; Dervishi, L.; Doğrusöz, Uğur; Zhou, W.; Shen, H.; Laird, P. W.; Way, G. P.; Greene, C. S.; Liang, H.; Xiao, Y.; Wang, C.; Iavarone, A.; Berger, A. H.; Bivona, T. G.; Lazar, A. J.; Hammer, G. D.; Giordano, T.; Kwong, L. N.; McArthur, G.; Huang, C.; Tward, A. D.; Frederick, M. J.; McCormick, F.; Meyerson, M.; Caesar-Johnson, S. J.; Demchok, J. A.; Felau, I.; Kasapi, M.; Ferguson, M. L.; Hutter, C. M.; Sofia, H. J.; Tarnuzzer, R.; Wang, Z.; Yang, L.; Zenklusen, J. C.; Zhang, J. J.; Chudamani, S.; Liu, J.; Lolla, L.; Naresh, R.; Pihl, T.; Sun, Q.; Wan, Y.; Wu, Y.; Cho, J.; DeFreitas, T.; Frazer, S.; Gehlenborg, N.; Getz, G.; Heiman, D. I.; Kim, J.; Lawrence, M. S.; Lin, P.; Meier, S.; Noble, M. S.; Saksena, G.; Voet, D.; Zhang, H.; Bernard, B.; Chambwe, N.; Dhankani, V.; Knijnenburg, T.; Kramer, R.; Leinonen, K.; Liu, Y.; Miller, M.; Reynolds, S.; Shmulevich, I.; Thorsson, V.; Zhang, W.; Akbani, R.; Broom, B. M.; Hegde, A. M.; Ju, Z.; Kanchi, R. S.; Korkut, A.; Li, J.; Liang, H.; Ling, S.; Liu W.; Lu, Y.; Mills, G. B.; Ng, K. -S.; Rao, A.; Ryan, M.; Wang, J.; Weinstein, J. N.; Zhang, J.; Abeshouse, A.; Armenia, J.; Chakravarty, D.; Chatila, W. K.; de, Bruijn, I.; Gao, J.; Gross, B. E.; Heins, Z. J.; Kundra, R.; La, K.; Ladanyi, M.; Luna, A.; Nissan, M. G.; Ochoa, A.; Phillips, S. M.; Reznik, E.; Sanchez-Vega, F.; Sander, C.; Schultz, N.; Sheridan, R.; Sumer, S. O.; Sun, Y.; Taylor, B. S.; Wang, J.; Zhang, H.; Anur, P.; Peto, M.; Spellman, P.; Benz, C.; Stuart, J. M.; Wong, C. K.; Yau, C.; Hayes, D. N.; Parker, J. S.; Wilkerson, M. D.; Ally, A.; Balasundaram, M.; Bowlby, R.; Brooks, D.; Carlsen, R.; Chuah, E.; Dhalla, N.; Holt, R.; Jones, S. J. M.; Kasaian, K.; Lee, D.; Ma, Y.; Marra, M. A.; Mayo, M.; Moore, R. A.; Mungall, A. J.; Mungall, K.; Robertson, A. G.; Sadeghi, S.; Schein, J. E.; Sipahimalani, P.; Tam, A.; Thiessen, N.; Tse, K.; Wong, T.; Berger, A. C.; Beroukhim, R.; Cherniack, A. D.; Cibulskis, C.; Gabriel, S. B.; Gao, G. F.; Ha, G.; Meyerson, M.; Schumacher, S. E.; Shih, J.; Kucherlapati, M. H.; Kucherlapati, R. S.; Baylin, S.; Cope, L.; Danilova, L.; Bootwalla, M. S.; Lai, P. H.; Maglinte, D. T.; Van, Den, Berg, D. J.; Weisenberger, D. J.; Auman, J. T.; Balu, S.; Bodenheimer, T.; Fan, C.; Hoadley, K. A.; Hoyle, A. P.; Jefferys, S. R.; Jones, C. D.; Meng, S.; Mieczkowski, P. A.; Mose, L. E.; Perou, A. H.; Perou, C. M.; Roach, J.; Shi, Y.; Simons, J. V.; Skelly, T.; Soloway, M. G.; Tan, D.; Veluvolu, U.; Fan, H.; Hinoue, T.; Laird, P. W.; Shen, H.; Zhou, W.; Bellair, M.; Chang, K.; Covington, K.; Creighton, C. J.; Dinh, H.; Doddapaneni, H.; Donehower, L. A.; Drummond, J.; Gibbs, R. A.; Glenn, R.; Hale, W.; Han, Y.; Hu, J.; Korchina, V.; Lee, S.; Lewis, L.; Li, W.; Liu, X.; Morgan, M.; Morton, D.; Muzny, D.; Santibanez, J.; Sheth, M.; Shinbrot, E.; Wang, L.; Wang, M.; Wheeler, D. A.; Xi, L.; Zhao, F.; Hess, J.; Appelbaum, E. L.; Bailey, M.; Cordes, M. G.; Ding, L.; Fronick, C. C.; Fulton, L. A.; Fulton, R. S.; Kandoth, C.; Mardis, E. R.; McLellan, M. D.; Miller, C. A.; Schmidt, H. K.; Wilson, R. K.; Crain, D.; Curley, E.; Gardner, J.; Lau, K.; Mallery, D.; Morris, S.; Paulauskis, J.; Penny, R.; Shelton, C.; Shelton, T.; Sherman, M.; Thompson, E.; Yena, P.; Bowen, J.; Gastier-Foster, J. M.; Gerken, M.; Leraas, K. M.; Lichtenberg, T. M.; Ramirez, N. C.; Wise, L.; Zmuda, E.; Corcoran, N.; Costello, T.; Hovens, C.; Carvalho, A. L.; de, Carvalho, A. C.; Fregnani, J. H.; Longatto-Filho, A.; Reis, R. M.; Scapulatempo-Neto, C.; Silveira, H. C. S.; Vidal, D. O.; Burnette, A.; Eschbacher, J.; Hermes, B.; Noss, A.; Singh, R.; Anderson, M. L.; Castro, P. D.; Ittmann, M.; Huntsman, D.; Kohl, B.; Le, X.; Thorp, R.; Andry, C.; Duffy, E. R.; Lyadov, V.; Paklina, O.; Setdikova, G.; Shabunin, A.; Tavobilov, M.; McPherson, C.; Warnick, R.; Berkowitz, R.; Cramer, D.; Feltmate, C.; Horowitz, N.; Kibel, A.; Muto, M.; Raut, C. P.; Malykh, A.; Barnholtz-Sloan, J. S.; Barrett, W.; Devine, K.; Fulop, J.; Ostrom, Q. T.; Shimmel, K.; Wolinsky, Y.; Sloan, A. E.; De, Rose, A.; Giuliante, F.; Goodman, M.; Karlan, B. Y.; Hagedorn, C. H.; Eckman, J.; Harr, J.; Myers, J.; Tucker, K.; Zach, L. A.; Deyarmin, B.; Hu, H.; Kvecher, L.; Larson, C.; Mural, R. J.; Somiari, S.; Vicha, A.; Zelinka, T.; Bennett, J.; Iacocca, M.; Rabeno, B.; Swanson, P.; Latour, M.; Lacombe, L.; Têtu, B.; Bergeron, A.; McGraw, M.; Staugaitis, S. M.; Chabot, J.; Hibshoosh, H.; Sepulveda, A.; Su, T.; Wang, T.; Potapova, O.; Voronina, O.; Desjardins, L.; Mariani, O.; Roman-Roman, S.; Sastre, X.; Stern, M. -H.; Cheng, F.; Signoretti, S.; Berchuck, A.; Bigner, D.; Lipp, E.; Marks, J.; McCall, S.; McLendon, R.; Secord, A.; Sharp, A.; Behera, M.; Brat, D. J.; Chen, A.; Delman, K.; Force, S.; Khuri, F.; Magliocca, K.; Maithel, S.; Olson, J. J.; Owonikoko, T.; Pickens, A.; Ramalingam, S.; Shin, D. M.; Sica, G.; Van, Meir, E. G.; Zhang, H.; Eijckenboom, W.; Gillis, A.; Korpershoek, E.; Looijenga, L.; Oosterhuis, W.; Stoop, H.; van, Kessel, K. E.; Zwarthoff, E. C.; Calatozzolo, C.; Cuppini, L.; Cuzzubbo, S.; DiMeco, F.; Finocchiaro, G.; Mattei, L.; Perin, A.; Pollo, B.; Chen, C.; Houck, J.; Lohavanichbutr, P.; Hartmann, A.; Stoehr, C.; Stoehr, R.; Taubert, H.; Wach, S.; Wullich, B.; Kycler, W.; Murawa, D.; Wiznerowicz, M.; Chung, K.; Edenfield, W. J.; Martin, J.; Baudin, E.; Bubley, G.; Bueno, R.; De, Rienzo, A.; Richards, W. G.; Kalkanis, S.; Mikkelsen, T.; Noushmehr, H.; Scarpace, L.; Girard, N.; Aymerich, M.; Campo, E.; Giné, E.; Guillermo, A. L.; Van, Bang, N.; Hanh, P. T.; Phu, B. D.; Tang, Y.; Colman, H.; Evason, K.; Dottino, P. R.; Martignetti, J. A.; Gabra, H.; Juhl, H.; Akeredolu, T.; Stepa, S.; Hoon, D.; Ahn, K.; Kang, K. J.; Beuschlein, F.; Breggia, A.; Birrer, M.; Bell, D.; Borad, M.; Bryce, A. H.; Castle, E.; Chandan, V.; Cheville, J.; Copland, J. A.; Farnell, M.; Flotte, T.; Giama, N.; Ho, T.; Kendrick, M.; Kocher, J. -P.; Kopp, K.; Moser, C.; Nagorney, D.; O'Brien, D.; O'Neill, B. P.; Patel, T.; Petersen, G.; Que, F.; Rivera, M.; Roberts, L.; Smallridge, R.; Smyrk, T.; Stanton, M.; Thompson, R. H.; Torbenson, M.; Yang, J. D.; Zhang, L.; Brimo, F.; Ajani, J. A.; Gonzalez, A. M. A.; Behrens, C.; Bondaruk, J.; Broaddus, R.; Czerniak, B.; Esmaeli, B.; Fujimoto, J.; Gershenwald, J.; Guo, C.; Lazar, A. J.; Logothetis, C.; Meric-Bernstam, F.; Moran, C.; Ramondetta, L.; Rice, D.; Sood, A.; Tamboli, P.; Thompson, T.; Troncoso, P.; Tsao, A.; Wistuba, I.; Carter, C.; Haydu, L.; Hersey, P.; Jakrot, V.; Kakavand, H.; Kefford, R.; Lee, K.; Long, G.; Mann, G.; Quinn, M.; Saw, R.; Scolyer, R.; Shannon, K.; Spillane, A.; Stretch, J.; Synott, M.; Thompson, J.; Wilmott, J.; Al-Ahmadie, H.; Chan, T. A.; Ghossein, R.; Gopalan, A.; Levine, D. A.; Reuter, V.; Singer, S.; Singh, B.; Tien, N. V.; Broudy, T.; Mirsaidi, C.; Nair, P.; Drwiega, P.; Miller, J.; Smith, J.; Zaren, H.; Park, J. -W.; Hung, N. P.; Kebebew, E.; Linehan, W. M.; Metwalli, A. R.; Pacak, K.; Pinto, P. A.; Schiffman, M.; Schmidt, L. S.; Vocke, C. D.; Wentzensen, N.; Worrell, R.; Yang, H.; Moncrieff, M.; Goparaju, C.; Melamed, J.; Pass, H.; Botnariuc, N.; Caraman, I.; Cernat, M.; Chemencedji, I.; Clipca, A.; Doruc, S.; Gorincioi, G.; Mura, S.; Pirtac, M.; Stancul, I.; Tcaciuc, D.; Albert, M.; Alexopoulou, I.; Arnaout, A.; Bartlett, J.; Engel, J.; Gilbert, S.; Parfitt, J.; Sekhon, H.; Thomas, G.; Rassl, D. M.; Rintoul, R. C.; Bifulco, C.; Tamakawa, R.; Urba, W.; Hayward, N.; Timmers, H.; Antenucci, A.; Facciolo, F.; Grazi, G.; Marino, M.; Merola, R.; de, Krijger, R.; Gimenez-Roqueplo, A. -P.; Piché, A.; Chevalier, S.; McKercher, G.; Birsoy, K.; Barnett, G.; Brewer, C.; Farver, C.; Naska, T.; Pennell, N. A.; Raymond, D.; Schilero, C.; Smolenski, K.; Williams, F.; Morrison, C.; Borgia, J. A.; Liptay, M. J.; Pool, M.; Seder, C. W.; Junker, K.; Omberg, L.; Dinkin, M.; Manikhas, G.; Alvaro, D.; Bragazzi, M. C.; Cardinale, V.; Carpino, G.; Gaudio, E.; Chesla, D.; Cottingham, S.; Dubina, M.; Moiseenko, F.; Dhanasekaran, R.; Becker, K. -F.; Janssen, K. -P.; Slotta-Huspenina, J.; Abdel-Rahman, M. H.; Aziz, D.; Bell, S.; Cebulla, C. M.; Davis, A.; Duell, R.; Elder, J. B.; Hilty, J.; Kumar, B.; Lang, J.; Lehman, N. L.; Mandt, R.; Nguyen, P.; Pilarski, R.; Rai, K.; Schoenfield, L.; Senecal, K.; Wakely, P.; Hansen, P.; Lechan, R.; Powers, J.; Tischler, A.; Grizzle, W. E.; Sexton, K. C.; Kastl, A.; Henderson, J.; Porten, S.; Waldmann, J.; Fassnacht, M.; Asa, S. L.; Schadendorf, D.; Couce, M.; Graefen, M.; Huland, H.; Sauter, G.; Schlomm, T.; Simon, R.; Tennstedt, P.; Olabode, O.; Nelson, M.; Bathe, O.; Carroll, P. R.; Chan, J. M.; Disaia, P.; Glenn, P.; Kelley, R. K.; Landen, C. N.; Phillips, J.; Prados, M.; Simko, J.; Smith-McCune, K.; VandenBerg, S.; Roggin, K.; Fehrenbach, A.; Kendler, A.; Sifri, S.; Steele, R.; Jimeno, A.; Carey, F.; Forgie, I.; Mannelli, M.; Carney, M.; Hernandez, B.; Campos, B.; Herold-Mende, C.; Jungk, C.; Unterberg, A.; von, Deimling, A.; Bossler, A.; Galbraith, J.; Jacobus, L.; Knudson, M.; Knutson, T.; Ma, D.; Milhem, M.; Sigmund, R.; Godwin, A. K.; Madan, R.; Rosenthal, H. G.; Adebamowo, C.; Adebamowo, S. N.; Boussioutas, A.; Beer, D.; Giordano, T.; Mes-Masson, A. -M.; Saad, F.; Bocklage, T.; Landrum, L.; Mannel, R.; Moore, K.; Moxley, K.; Postier, R.; Walker, J.; Zuna, R.; Feldman, M.; Valdivieso, F.; Dhir, R.; Luketich, J.; Pinero, E. M. M.; Quintero-Aguilo, M.; Carlotti, C. G.; Jr.; Dos, Santos, J. S.; Kemp, R.; Sankarankuty, A.; Tirapelli, D.; Catto, J.; Agnew, K.; Swisher, E.; Creaney, J.; Robinson, B.; Shelley, C. S.; Godwin, E. 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Genetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tumor types. Using mutations, copy-number changes, mRNA expression, gene fusions and DNA methylation in 9,125 tumors profiled by The Cancer Genome Atlas (TCGA), we analyzed the mechanisms and patterns of somatic alterations in ten canonical pathways: cell cycle, Hippo, Myc, Notch, Nrf2, PI-3-Kinase/Akt, RTK-RAS, TGFβ signaling, p53 and β-catenin/Wnt. We charted the detailed landscape of pathway alterations in 33 cancer types, stratified into 64 subtypes, and identified patterns of co-occurrence and mutual exclusivity. Eighty-nine percent of tumors had at least one driver alteration in these pathways, and 57% percent of tumors had at least one alteration potentially targetable by currently available drugs. Thirty percent of tumors had multiple targetable alterations, indicating opportunities for combination therapy. An integrated analysis of genetic alterations in 10 signaling pathways in >9,000 tumors profiled by TCGA highlights significant representation of individual and co-occurring actionable alterations in these pathways, suggesting opportunities for targeted and combination therapies.